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Main Authors: Haghofer, Andreas, Parlak, Eda, Bartel, Alexander, Donovan, Taryn A., Assenmacher, Charles-Antoine, Bolfa, Pompei, Dark, Michael J., Fuchs-Baumgartinger, Andrea, Klang, Andrea, Jäger, Kathrin, Klopfleisch, Robert, Merz, Sophie, Richter, Barbara, Schulman, F. Yvonne, Janout, Hannah, Ganz, Jonathan, Scharinger, Josef, Aubreville, Marc, Winkler, Stephan M., Kiupel, Matti, Bertram, Christof A.
Format: Preprint
Published: 2023
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Online Access:https://arxiv.org/abs/2309.15031
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author Haghofer, Andreas
Parlak, Eda
Bartel, Alexander
Donovan, Taryn A.
Assenmacher, Charles-Antoine
Bolfa, Pompei
Dark, Michael J.
Fuchs-Baumgartinger, Andrea
Klang, Andrea
Jäger, Kathrin
Klopfleisch, Robert
Merz, Sophie
Richter, Barbara
Schulman, F. Yvonne
Janout, Hannah
Ganz, Jonathan
Scharinger, Josef
Aubreville, Marc
Winkler, Stephan M.
Kiupel, Matti
Bertram, Christof A.
author_facet Haghofer, Andreas
Parlak, Eda
Bartel, Alexander
Donovan, Taryn A.
Assenmacher, Charles-Antoine
Bolfa, Pompei
Dark, Michael J.
Fuchs-Baumgartinger, Andrea
Klang, Andrea
Jäger, Kathrin
Klopfleisch, Robert
Merz, Sophie
Richter, Barbara
Schulman, F. Yvonne
Janout, Hannah
Ganz, Jonathan
Scharinger, Josef
Aubreville, Marc
Winkler, Stephan M.
Kiupel, Matti
Bertram, Christof A.
contents Variation in nuclear size and shape is an important criterion of malignancy for many tumor types; however, categorical estimates by pathologists have poor reproducibility. Measurements of nuclear characteristics (morphometry) can improve reproducibility, but manual methods are time consuming. The aim of this study was to explore the limitations of estimates and develop alternative morphometric solutions for canine cutaneous mast cell tumors (ccMCT). We assessed the following nuclear evaluation methods for measurement accuracy, reproducibility, and prognostic utility: 1) anisokaryosis (karyomegaly) estimates by 11 pathologists; 2) gold standard manual morphometry of at least 100 nuclei; 3) practicable manual morphometry with stratified sampling of 12 nuclei by 9 pathologists; and 4) automated morphometry using a deep learning-based segmentation algorithm. The study dataset comprised 96 ccMCT with available outcome information. The study dataset comprised 96 ccMCT with available outcome information. Inter-rater reproducibility of karyomegaly estimates was low ($κ$ = 0.226), while it was good (ICC = 0.654) for practicable morphometry of the standard deviation (SD) of nuclear size. As compared to gold standard manual morphometry (AUC = 0.839, 95% CI: 0.701 - 0.977), the prognostic value (tumor-specific survival) of SDs of nuclear area for practicable manual morphometry (12 nuclei) and automated morphometry were high with an area under the ROC curve (AUC) of 0.868 (95% CI: 0.737 - 0.991) and 0.943 (95% CI: 0.889 - 0.996), respectively. This study supports the use of manual morphometry with stratified sampling of 12 nuclei and algorithmic morphometry to overcome the poor reproducibility of estimates.
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publishDate 2023
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spellingShingle Nuclear Pleomorphism in Canine Cutaneous Mast Cell Tumors: Comparison of Reproducibility and Prognostic Relevance between Estimates, Manual Morphometry and Algorithmic Morphometry
Haghofer, Andreas
Parlak, Eda
Bartel, Alexander
Donovan, Taryn A.
Assenmacher, Charles-Antoine
Bolfa, Pompei
Dark, Michael J.
Fuchs-Baumgartinger, Andrea
Klang, Andrea
Jäger, Kathrin
Klopfleisch, Robert
Merz, Sophie
Richter, Barbara
Schulman, F. Yvonne
Janout, Hannah
Ganz, Jonathan
Scharinger, Josef
Aubreville, Marc
Winkler, Stephan M.
Kiupel, Matti
Bertram, Christof A.
Computer Vision and Pattern Recognition
Variation in nuclear size and shape is an important criterion of malignancy for many tumor types; however, categorical estimates by pathologists have poor reproducibility. Measurements of nuclear characteristics (morphometry) can improve reproducibility, but manual methods are time consuming. The aim of this study was to explore the limitations of estimates and develop alternative morphometric solutions for canine cutaneous mast cell tumors (ccMCT). We assessed the following nuclear evaluation methods for measurement accuracy, reproducibility, and prognostic utility: 1) anisokaryosis (karyomegaly) estimates by 11 pathologists; 2) gold standard manual morphometry of at least 100 nuclei; 3) practicable manual morphometry with stratified sampling of 12 nuclei by 9 pathologists; and 4) automated morphometry using a deep learning-based segmentation algorithm. The study dataset comprised 96 ccMCT with available outcome information. The study dataset comprised 96 ccMCT with available outcome information. Inter-rater reproducibility of karyomegaly estimates was low ($κ$ = 0.226), while it was good (ICC = 0.654) for practicable morphometry of the standard deviation (SD) of nuclear size. As compared to gold standard manual morphometry (AUC = 0.839, 95% CI: 0.701 - 0.977), the prognostic value (tumor-specific survival) of SDs of nuclear area for practicable manual morphometry (12 nuclei) and automated morphometry were high with an area under the ROC curve (AUC) of 0.868 (95% CI: 0.737 - 0.991) and 0.943 (95% CI: 0.889 - 0.996), respectively. This study supports the use of manual morphometry with stratified sampling of 12 nuclei and algorithmic morphometry to overcome the poor reproducibility of estimates.
title Nuclear Pleomorphism in Canine Cutaneous Mast Cell Tumors: Comparison of Reproducibility and Prognostic Relevance between Estimates, Manual Morphometry and Algorithmic Morphometry
topic Computer Vision and Pattern Recognition
url https://arxiv.org/abs/2309.15031